Deranged Physiologyis a slowly growing archive of discussions and study notes relevant (or if not relevant, then at least interesting) to the practice of intensive care medicine. The content provides an introduction to the fundamental themes in intensive care: mechanical ventilation, vasopressors, electrolyte management, hemodynamic monitoring, dialysis, and so forth. Attention is directed at equipment in intensive care, and there are attempts to revisit interesting pharmacology and physiology. The aim of this resource is to supplement the bedside teaching of senior staff, and to consolidate resources for intensive care trainees in the initial stages of their training.

An adverse drug event occurs during drug therapy but does not necessarily have any causal relationship with the drug, whereas an adverse drug reaction is directly related to the drug and occurs in the course of its appropriate use.

Interactions between drugs can be classified as pharmacokinetic and pharmacodynamic. Pharmacodynamic drug-drug interactions are briefly described in another chapter. Here, the focus is on the mechanisms by which drugs interfere with each other's absorption, distribution, metabolism and elimination.

Interactions between drugs can be classified as pharmacokinetic or pharmacodynamic. The pharmacodynamic interactions of drug-on-drug can be divided into three broad groups: interference with drug effects on receptor function, interference with a physiological control process, and additive or opposing physiological effects. To elaborate on these is the objective of this chapter.

Human populations express significant genetic polymorphism. This polymorphism extends to drug receptor targets, secondary messenger system and other homeostatic or regulatory pathways. Pharmacogenetics is the study of variability in drug response due to these inherited features. Examples of pharmacogenetic disorders include malignant hyperthermia, G6PD, porphyria and atypical plasma cholinesterase.

Human populations express significant genetic polymorphism. This polymorphism extends to drug receptor targets, secondary messenger system and other homeostatic or regulatory pathways. Pharmacogenetics is the study of variability in drug response due to these inherited features. Examples of pharmacogenetic disorders include malignant hyperthermia, G6PD, porphyria and atypical plasma cholinesterase.

In summary, one can say that infants and neonates are slow to absorb, slow to metabolise and slow to excrete all drugs, and that this gradually changes to more adult-like levels over the course of the first year of life. Pharmacodynamic alterations can be generally summarised as "more sensitive to everything".

Toxicology of childhood differs from adult toxicology on several key issues. In both scenarios, the patient is frequently uncooperative and history is often cluded, leading to empirical decisionmaking. In children, the situation is complicated by their tendency to compensate readily up to a certain cliff's edge, and then to collapse in a spectacular manner. Most of the routine toxicological primary survey is valid in the paediatric setting.

This chapter answers parts from Section D(iii) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe alterations to drug response due to physiological change, with particular reference to ...

In brief, old age affects drug absorption, distribution and elimination in a manner which can be suimmarised by the term "worse". Rarely is anything pharmacologically better in the elderly. They are reluctant to absorb drugs enterally, they are sluggish metabolisers, they more susceptible to side effects and their renal clearance is usually delayed, increasing the half life of most drugs. To say nothing of the tendency of physicians to challenge these physiologically fragile individuals with polypharmacy cocktails.

One cannot increase in body mass to three or four times the expected norm and still expect to have a normal response to drugs. The pharmacokinetic and pharmacodynamic changes associated with obesity are often surprisingly in the direction of increased function, for instance increased gastric emptying rate, increased hepatic clearance, increased GFR and renal clearance, and increased soluble enzyme activity. A large volume of adipose tissue increases the apparent volume of distribution for lipophilic drugs and increases their half-life. Everything is pharmacokinetically different, and dosing is made more difficult by the fact that the equations which predict lean body mass and ideal body weight become less and less accurate with increasing BMI.

Pregnancy results in several pharmacokinetic and pharmacodynamic changes. Oral administration is affected by delayed gastric emptying; distribution is affected by changes in the fat and water content of the body, and metabolism is afected by changes in hepatic blood flow and enzyme activity. Clearance of many substances is increased by the increased glomerular filtration rate. Pharmacodynamic changes are also numerous, eg. increased sensitivity to both local and general anaesthetics. Discussion of adverse effects and dosing adjustments must take into account toxicity to the foetus.

The College, in their model answer to Question 1 from the second paper of 2014, have constructed an excellent resuscitation protocol, which does not afford this author very much room for improvement.One can merely summarise their model, and expand upon it with references. To be clear, this approach is not "Early Goal-Directed Therapy". Protocolised sepsis management may not be especially effective in reducing mortality (ProCESS, ARISE). Rather than a protocol, this is a stepwise method to tailor a bespoke response to septic shock for individual patients, which branches from simple to advanced management options.

For the patient whose inspiratory flow rate exceeds even the generous threshold of Venturi masks, high flow nasal oxygen is an excellent option. Though the first paper to describe these devices (Dewan & Bell, 1994) gave us this terminology, subsequent authors have occasionally referred to these devices as "high flow nasal cannulae" or "high flow nasal oxygen", because presumably the word "prongs" is somehow uncivilized or intrinsically comical. All CICM trainees will be familiar with the device - it is a single-limb circuit which connects a gas blender to a heater/humidifier, and then funnels a mixture of oxygen and air into the patient, essentially using their respiratory system as a PEEP valve.